Project Description The hypothesis of this proposal is that multivalent vaccines can be generated against enterotoxigenic Escherichia coli (ETEC) and Campylobacter jejuni by conjugation of LTB and antigenically distinct colonization factor antigens (CFA's or fimbriae) from ETEC to the major capsule types of C. jejuni. C. jejuni is unusual for an enteric pathogen in that is produces a polysaccharide capsule. There is evidence that a vaccine consisting of a C. jejuni capsule conjugated to CRM197, a diphtheria toxoid used in licensed conjugate vaccines, was protective against diarrheal disease in non-human primates (NHP). Evidence also exists that fimbrial tip adhesins, which are less antigenically diverse than the major fimbrial subunits, are also protective in NHP's and humans. Conjugation of these ETEC proteins to C. jejuni capsules provides a novel approach to development of multivalent, broad-spectrum vaccines against two major causes of bacterial diarrhea. /project narrative Enterotoxigenic Escherichia coli (ETEC) and Campylobacter jejuni (CJ) are major causes of diarrheal disease worldwide. ETEC and CJ are both serious threats to western travelers and young children in resource limited countries, and there are no licensed vaccines available for either agent. This project combines two novel vaccine strategies against these two pathogens with the aim of a broad-spectrum vaccine. Polysaccharide capsules from major serotypes of CJ will be conjugated to antigenically distinct ETEC fimbrial tip subunits and the binding subunit of the heat labile enterotoxin, LTB. Multiple conjugates could be combined into a multi-valent vaccine that would afford protection against the major antigenic variants of both pathogens. Relevance: Enterotoxigenic Escherichia coli (ETEC) and Campylobacter jejuni (CJ) are major causes of diarrheal disease worldwide. ETEC and CJ are both serious threats to western travelers and young children in resource limited countries, and there are no licensed vaccines available for either agent. This project combines two novel vaccine strategies against these two pathogens with the aim of a broad-spectrum vaccine. Polysaccharide capsules from major serotypes of CJ will be conjugated to antigenically distinct ETEC fimbrial tip subunits and the binding subunit of the heat labile enterotoxin, LTB. Multiple conjugates could be combined into a multi-valent vaccine that would afford protection against the major antigenic variants of both pathogens.